Compositions comprising biguanide compound and diol surfactant

ABSTRACT

Antimicrobial compositions are described comprising a least one biguanide compound and at least one hydrocarbon surfactant comprising a saturated or unsaturated C 2 -C 4  diol moiety and optionally further comprising alkoxy groups. In some embodiments, the composition further comprises an aqueous or hydrophilic liquid carrier. In favored embodiments, the diol surfactant is present in an amount such that the antimicrobial activity of the biguanide antimicrobial compound is improved. Also described are articles comprising the described antimicrobial composition and methods of use of the antimicrobial composition.

SUMMARY

Presently described is an antimicrobial composition comprising a leastone biguanide compound and at least one hydrocarbon surfactantcomprising a saturated or unsaturated C₂-C₄ diol moiety, optionallyfurther comprising alkoxy groups. In some embodiments, the compositionfurther comprises an aqueous or hydrophilic liquid carrier.

The surfactant typically has the formula

wherein L is a covalent bond or a saturated or unsaturated C₁-C₂ moiety,R is independently a straight chained or branched C₁-C₁₂ alkyl moiety, Xis independently a C₂-C₄ alkoxy, and m+n ranges from 0 to about 50.

In favored embodiments, the diol surfactant is present in an amount suchthat the antimicrobial activity of the biguanide antimicrobial compoundis improved.

Also described are articles comprising the described antimicrobialcomposition. In some embodiments, the composition is absorbed ordisposed on a carrier substrate.

Also described are methods of use comprising providing the describedantimicrobial composition and applying the composition to a surface.

DETAILED DESCRIPTION

The compositions described herein comprise an antimicrobial.“Antimicrobial” means a chemical agent other than an “enhancer” asdescribed herein that kills pathogenic and non-pathogenicmicroorganisms. When utilized to kill or prevent the growth ofmicroorganism on a mammal, such as humans, the term antimicrobial can besynonymous with the term antiseptic. Antiseptics generally interferemore broadly with the cellular metabolism and/or the cell envelope.

The antimicrobial composition comprises an effective amount of one ormore biguanide compounds. The biguanide compound is generally consideredthe main active component of the composition. As used herein the termbiguanide includes bisbiguanides.

In some embodiments, the biguanide compound can be represented by theformula:

R—NHC(NH)NHC(NH)NH(CH₂)_(n)NHC(NH)NHC(NH)NH—R

where n=3-10, preferably 4-8, and most preferably 6; and R is a C₄-C₁₈branched or straight chain alkyl, C₆-C₁₂ aryl or alkaryl, each of whichmay be optionally substituted in available positions by halogen. In someembodiments, the molecular weight of such biguanide compound is nogreater than 1000, 900, 800, 700, or 600 g/mole.

One preferred compound of this class is chlorhexidine. This may bepresent as the free base but is typically present as a disalt ofacetate, gluconate, lactate, methosulfate (CH₃OSO₃ ⁻), or a halide orcombinations thereof. Diacetate, digluconate, dilactate, anddimethosulfate salts can be preferred since these salts exhibit asolubility in aqueous fluid in excess of 1 g/100 ml. For example, thesolubility of the digluconate salt is 20 g/100 ml and that of thediacetate is 1.9 g/100 ml. The most common compound is chlorhexidinedigluconate (CHG). Other anions may be useful. The counter ion typicallyensures sufficient solubility in aqueous fluid.

In one embodiment, the biguanide compound can be characterized as apolybiguanide. Compounds of this class can be represented by theformula:

X—R¹—[NHC(NH)NHC(NH)NH—R²]_(n)—X

where R¹ and R² are bridging groups such as alkylene groups typicallyhaving 2 to 10 carbons atoms, 4 to 8 carbons atom, and most typically 6carbon atoms. The alkylene bridging groups can be optionally substitutedin available positions with halogen, hydroxyl, or phenyl groups. X is aterminal group and is typically an amine, amine salt, or a dicyandiamidegroup. The number of repeat units, “n” can range from 2 to about 50. Insome embodiments, the average molecular weight (Mw) of such biguanidecompounds can range up to 10,000 g/mole. In other embodiments, theaverage molecular weight (Mw) of such biguanide compounds is no greaterthan 5,000 or 1,000 g/mole. A preferred compound of this class ispolyhexamethylene biguanide (PHMB) commercially available as Cosmocil CQfrom Lonza Chemicals, Allendale, N.J.

One or more biguanide compounds are present in the composition in aneffective amount to provide the desired antimicrobial properties.

In typical embodiments, the composition comprises at least oneantimicrobial biguanide compound and at least one saturated orunsaturated (e.g acetylenic) C₂-C₄ diol surfactant dissolved ordispersed in an aqueous liquid carrier. By “aqueous” it is meant thatthe liquid carrier comprises at least 50, 60, 70, 80 wt-% to 100 wt-%water.

In other embodiments, the composition comprises at least oneantimicrobial biguanide compound and at least one saturated orunsaturated (e.g. acetylenic) C₂-C₄ diol surfactant dissolved ordispersed in a hydrophilic liquid carrier. By “hydrophilic liquidcarrier” it is meant that the liquid carrier comprises greater than 50,60, 70, 80 wt-% of a liquid carrier other than water. In someembodiments, the water content is less than 20, 15, 10 or 5 wt-%. Intypical embodiments, the water (when present) and hydrophilic liquid aremiscible at 23° C. forming a stable continuous liquid phase.

The hydrophilic liquid carrier may comprise liquids which may beconsidered “an additional enhancer” provided that the inclusion of suchdoes not mask the enhancing effect of the saturated or unsaturated (e.g.acetylenic) C₂-C₄ diol surfactant. For example, if the combination ofbiguanide antimicrobial and other enhancer has a greater efficacy thanthe combination of biguanide and saturated or unsaturated (e.g.acetylenic) C₂-C₄ diol surfactant, the enhancing effect of the diolsurfactant is typically not detectable. The enhancer component mayinclude an alpha-hydroxy acid, a beta-hydroxy acid, other carboxylicacids, a (C1-C4)alkyl carboxylic acid, a (C6-C12)aryl carboxylic acid, a(C6-C12)aralkyl carboxylic acid, a (C6-C16)alkaryl carboxylic acid, achelator, a phenolic compound (such as certain antioxidants andparabens), a (C1-C10)monohydroxy alcohol, or a glycol ether (i.e., etherglycol). Various combinations of enhancers can be used if desired.

In some embodiments, the hydrophilic liquid carrier comprises amonohydroxy alcohol having 1-10 carbon atoms. This includes the lower(i.e., C1-C4) monohydroxy alcohols (e.g., methanol, ethanol,isopropanol, and butanol) as well as longer chain (i.e., C5-C10)monohydroxy alcohols (e.g., isobutanol, t-butanol, octanol, anddecanol). In certain embodiments, the alcohols useful in thecompositions of the present invention are selected from the groupconsisting of methanol, ethanol, isopropyl alcohol, and mixturesthereof.

In some embodiments, at least one (e.g. short chain C1-C4) alcohol ispresent in a total amount of at least 0.5, 1, 2, 3, 4 or 5 wt-%. In someembodiments, the concentration of alcohol is no greater than 50, 40, 30,or 20 wt-% of the ready to use composition.

For certain applications, lower alcohols may not be preferred due to thestrong odor and potential for stinging and irritation. This can occurespecially at higher levels. In applications where stinging or burningis a concern, the concentration of (C1-C4) alcohols is preferably lessthan 20%, more preferably less than about 15%.

In one embodiment, longer chain (i.e., C5-C10) alcohols are present in atotal amount of at least 0.1, 0.25, 0.5 wt-% or 1.0%, based on the readyto use composition.

The (C5-C10) alcohols are typically present in a total amount of nogreater than 10, 5, 4, 3, or 2 wt-%, based on the total weight of theready to use composition.

In another embodiment, the hydrophilic liquid comprises an ether glycol.Exemplary ether glycols include those of the formula:

R′—O—(CH₂CHR″O)_(n)(CH₂CHR″O)H

wherein R′ is H, a (C1-C8) alkyl, a (C6-C12) aryl or a (C6-C12) aralkylor (C6-C12) alkaryl; and each R″ is independently =H, methyl, or ethyl;and n=0-5, preferably 1-3. Examples include 2 phenoxyethanol,dipropylene glycol, triethylene glycol, the line of products availableunder the trade designation DOWANOL DB (di(ethylene glycol) butylether), DOWANOL DPM (di(propylene glycol)monomethyl ether), and DOWANOLTPnB (tri(propylene glycol) monobutyl ether), as well as many othersavailable from Dow Chemical, Midland Mich.

In one embodiment, ether glycols are present in a total amount of atleast 0.1, 0.25, 0.5 wt-% or 1.0%, based on the ready to usecomposition. The ether glycols are typically present in a total amountof no greater than 20, 15, 10, 5, 4, 3, or 2 wt-%, based on the totalweight of the ready to use composition.

In yet another embodiment, the composition comprising at least onebiguanide antimicrobial compound and at least one (e.g. acetylenic) diolsurfactant typically but optionally diluted in a liquid medium, such aswater, can be applied to a carrier substrate such as nonwoven and dried.In this embodiment, the (i.e. dried) composition is disposed on thecarrier substrate. The enhanced antimicrobial can be reactivated byapplying an aqueous or hydrophilic liquid to the dried carriersubstrate.

The effective amount of biguanide antimicrobial compound is typically nogreater than about 5, 4, 3, 2, or 1 wt-% based on the total weight ofthe aqueous or hydrophilic composition. The effective amount is moretypically no greater than 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2 or 0.1wt.-% based on the total weight of the composition. In some embodiments,the effective amount may be as little as 0.09, 0.08, 0.07, 0.06, 0.05,0.04, 0.03, 0.02 or 0.01 wt.-%. In some embodiments, the effectiveamount may be as little as 0.009, 0.008, 0.007, 0.006, 0.005, 0.004,0.003, 0.002 or 0.001 wt-%. The composition described herein may howeverbe a concentrated composition that is typically diluted prior to use.Such concentrated compositions may comprise as much as 10 wt-% orgreater of biguanide compounds(s).

It will be appreciated by one of ordinary skill in the art that thelevels or ranges selected for the required or optional componentsdescribed herein will depend upon factors such as whether one isformulating a composition for direct use, or a concentrate for dilutionprior.

The compositions described here further comprise at least one surfactantcompound based on a saturated or unsaturated (e.g. acetylenic) diol or aderivative thereof. The saturated or unsaturated (e.g. acetylenic) diolsurfactant compound functions as an enhancer for the antimicrobial.“Enhancer” means a component that enhances the effectiveness of theantimicrobial component. The composition comprising both theantimicrobial component and the enhancer component provides improvedantimicrobial activity relative to these components being utilizedseparately. The enhancing effect can be with respect to the level ofkill, the speed of kill, and/or the spectrum of microorganisms killed.The enhancing effect may be evident with respect to some microorganismsand absent with respect to others. The enhancer effect is typicallysynergistic such that the composition as a whole displays an activitythat is greater than the sum of the activity of the antimicrobialcompound alone and the enhancer compound alone.

In some embodiments, the surfactant includes those according to thefollowing general structure:

wherein L is a covalent bond or a saturated or unsaturated C₁-C₂ moiety,R is independently a straight chained or branched C₁-C₁₂ alkyl moiety, Xis independently a C₂-C₄ alkoxy, and m+n ranges from 0 to about 50.

In some embodiments, the unsaturated moiety comprises a double bond orin other words L is an alkene moiety. In other embodiments, theunsaturated moiety comprises a triple bond and L is an alkyne moiety.

In some embodiments, the acetylenic diol compounds include thoseaccording to the following general structure:

wherein R is independently a C₁-C₁₂ alkyl which may be straight chainedor branched; X is independently selected from C₂-C₄ alkoxy (e.g. ethoxy,propoxy and butoxy); m+n is a number of moles of C₂-C₄ alkoxy and rangesfrom 0 to about 50.

In both of these structures preferably, R is a straight chained orbranched C₁-C₆ alkyl, X is an ethoxy moiety, and m+n is from 0 to about30. In some embodiments, m+n is 0. In other embodiments, m+n is at least1, 2, or 3. In some embodiments, m+n is no greater than 20, 15, or 10.

Various acetylenic diol surfactants are commercially available under thetrade designation SURFYNOL (ex. Air Products Inc., Allentown, Pa.)Non-limiting examples include SURFYNOL 104 which is described as2,4,7,9-tetramethyl-5-decyn-4,7-diol (also sometimes referred to as“tetramethyl decynediol”) (wherein m+n equals 0); as well as SURFYNOL82, described to be dimethyl octynediol (R is CH₂CH₃).

Other useful acetylenic diol compounds are ethoxylated derivates. Inthis embodiment, m, n and more typically are m+n is a number of moles ofethoxy.

Various ethoxylated derivatives of acetylenic diol surfactants arecommercially available under the trade under the trade designationSURFYNOL (ex. Air Products Inc., Allentown, Pa.) Non-limiting examplesinclude SURFYNOL 440, SURFYNOL 465 and SURFYNOL 485. More specifically,SURFYNOL 465 is described as being the reaction product of approximately10 moles of ethylene oxide (m+n equals 10) with 1 mole of tetramethyldecynediol. SURFYNOL 485 is described to be the reaction product ofapproximately 30 moles of ethylene oxide such that each X is ethoxy and(m+n equals 30) with 1 mole of tetramethyl decynediol. Other ethoxylatedacetylenic diols are available from Air Products under the tradenameDYNOL (e.g., DYNOL 604 and DYNOL 607).

A suitable alkane diol is 2,4,7,9-tetramethyldecane-4,7-diol availablefrom Air Products as “SURFYNOL AD01 SURFACTANT”. The total concentrationby weight of antimicrobial biguanide compound(s) relative to the totalconcentration of saturated or unsaturated (e.g. acetylenic) diolsurfactant(s) by weight can generally ranges from about 100:1 to about1:20. In some embodiments, the total concentration by weight ofbiguanide antimicrobial compound(s) relative to the total concentrationof saturated or unsaturated (e.g. acetylenic) diol surfactant(s) byweight is no greater than 75:1, 50:1, 25:1, 10:1, or 4:1. The weightratios are applicable for aqueous and hydrophilic compositions, as wellas for embodiments wherein the antimicrobial biguanide compound(s)together with the saturated or unsaturated (e.g. acetylenic) diolsurfactant(s) are present on a surface after removal (by evaporation oractive drying) of the aqueous or hydrophilic liquid medium.

In another embodiment, the composition may be a thickened aqueous gel ora thickened hydrophilic gel prepared by adding a thickener to theaqueous or hydrophilic liquid carrier.

The thickener system can include (e.g. soluble or swellable) organicpolymers or inorganic thixotropes such as silica gel, clays (such asbetonite, hectorite, montmorrillonite and the like), as well asorganically modified inorganic particulates materials, and the like.

The total concentration of the thickener system is typically less than10, 9, 8, 7, 5, 4, or 3 wt-% based on the total weight of the ready touse composition. The total concentration of the thickener is typicallyat least 0.5 wt-% or 1 wt-%, based on the total weight of the ready touse composition.

Biguanides, such as chlorhexidine and PHMB, are very basic and capableof forming multiple ionic bonds with anionic materials. For this reason,biguanide-containing compositions are generally free of anioiniccompounds that can result in precipitation of the antimicrobial. Forthis reason, thickener systems, if present, are typically based onnon-ionic and/or cationic polymers. Further, if additional surfactantsare present such surfactants are typically zwitterionic, very watersoluble, non-precipitating anionic emulsifiers, or non-ionic emulsifierssuch as poloxamers. If a salt is further included for stability or otherpurposes, preferably gluconate salts such as triethanolamine gluconateor sodium gluconate, are used.

The composition is generally free of anionic components such as anionicsurfactants and/or additional anionic antimicrobials, as well as halidesalts. As used herein, “free of” a particular constituent means that thecomposition contains less than 0.0001% wt. of the particularconstituent, and preferably the composition is essentially free of theparticular constituent.

Cationic polymeric thickeners include for example cationically modifiedcelluloses, quatemized natural amino-functional polymers, and polymersbased on ethylenically unsaturated monomers selected from the groupconsisting of acrylates, acrylamides, vinyl lactams, vinyl acetates,methyl vinyl ethers, styrene, and acrylonitrile.

Nonionic polymeric thickeners include for example modified celluloses,guar, xanthan gum, and other natural polymers such as polysaccharidesand proteins, associative polymers based on nonionic ethylenicallyunsaturated monomers wherein at least one comonomer has at least 16carbon atoms, and polymers based on ethylenically unsaturated monomersselected from the group consisting of acrylates, acrylamides, vinyllactams, vinyl acetate and its hydrolyzed derivatives, methyl vinylethers, styrene, and acrylonitrile.

A variety of cellulosic ethers are reported in the literature to besoluble in water. Materials in this class that are nonionic and havebeen shown to be useful include: methylhydroxypropylcellulose, availableas BENECEL MP 943 from Aqualon, Wilmington, Del.;hydroxypropylcellulose, available as KLUCEL (LF, GF, MF, HF) fromAqualon; hydroxybutylmethylcellulose (3.5 wt-% hydroxybutyl and 30 wt-%methoxyl) from Scientific Polymer Products, Ontario, N.Y.; andhydroxyethylcelluloses, available under the trade designation NATROSOLfrom Aqualon. Xanthan gum, guar, locust bean gum, and otherpolysaccharides may also be suitable. These polymers may be producedfrom plant sources or can be produced through microbial cell culture.Polyvinyl alcohol (PVA) also may be suitable. For example, PVA made frompolyvinyl acetate, which has been hydrolyzed to about 87%, is highlywater soluble at room temperature.

The gel can also be thickened using suitable emulsifiers such as alkylalcohols and polyethoxylated alkyl chain surfactants that effectivelythicken the composition. Examples include the Polawax, Behenyl TMS,Crodaphos CES, Cosmowax, and Crothix systems from Croda Inc.

The gels are typically thickened to achieve a viscosity in excess of 500cps, 1000 cps, 2000 cps, 3000 cps, 4000 cps, 5000 cps. Typically theviscosity in excess of 10,000 cps, more preferably greater than 25,000cps and most preferably greater than 50,000 cps.

Compositions of the present invention may additionally employ adjunctcomponents known in the art such as dyes, perfumes, fragrances,lubricants, thickening agents, stabilizers, skin penetration enhancers,preservatives, antioxidants, additional (cationic or non-ionic)antimicrobial, a flavoring agent (particularly for oral uses); providingthe inclusion of such adjunct components does not detract from thecombination of biguanide antimicrobial enhanced by the saturated orunsaturated (e.g. acetylene) diol surfactant.

Preferred compositions of the present invention exhibit good chemicalstability. This can be especially a concern with compounds that mayhydrolyze or undergo heat and/or light degradation such aschlorhexidine. The composition preferably retains an average of at least97% of the antimicrobial component after aging for 4 weeks at 40° C. ina sealed container beyond the initial 5-day equilibration period at 23°C.

The composition described herein can reduce and eliminate Staphylococcusaureus and Pseudomonas aeruginosa. Those of ordinary skill in the artwill readily determine when a composition provides antimicrobialactivity using assay and bacterial screening methods well known in theart. For example, the compositions can be evaluated utilizingAntimicrobial Efficacy Test described in the Examples Section. Briefly,a bacterial suspension is introduced into a liquid composition. After asufficient contact time, the sample containing the exposed bacteria iscollected, placed in neutralizing broth, a sample is taken and diluted,and plated on growth medium. The plated sample is incubated at anappropriate temperature and humidity for twenty four to forty-eighthours and the number of viable bacterial colonies growing on the plateis counted. Once colonies have been counted the reduction in the numberof bacteria caused by the test composition is readily determined.Bacterial reduction is generally reported as log to reduction determinedby the difference between the log₁₀ of the initial inoculum count (i.e.the control) and the log₁₀ of the inoculum count after exposure.

Compositions were tested as described in the Examples Section forantimicrobial activity against Staphylococcus aureus (Gram positive,strain number 15981) and Pseudomonas aeruginosa (Gram negative, AmericanType Culture Collection (ATCC) strain number 15442 or 9027). Preferredcompositions of the present invention also exhibit very rapidantimicrobial activity. In some embodiments, the compositions have anaverage of at least a 0.5, 1, 1.5 or 2 log reduction in test bacteria in15 seconds, 30 seconds or 60 seconds. In other embodiments, thecompositions have an average of at least a 2.5, 3, 3.5, 4, 4.5, 5 or 6log reduction in test bacteria in 15 seconds, 30 seconds or 60 seconds.

In some embodiments, the improvement by inclusion of the saturated orunsaturated (e.g. acetylenic) diol surfactant is 50%, 100%, 200%, 300%,400%, 500% or greater relative to the biguainde antimicrobial alone atthe same concentration (difference in log₁₀ reduction divided bycontrol)×100%. For example in one embodiment, 0.1 wt-% of CHG aloneprovided a log 10 reduction of 0.32; whereas when in combination withDYNOL, the log 10 reduction was in excess of 6; i.e. a 20× improvement(2000%).

In other embodiments, the composition described herein can reduce andeliminate (e.g. Pseudomonas aeruginosa) biofilms using assay andbacterial screening methods well known in the art. For example, thecompositions can be evaluated by use of a Minimum Biofilm EradicationConcentration device described in the Examples section. A biofilm is anaggregate of microorganisms that are adhered to each other on a surfacethrough an extracellular polymeric matrix.

The compositions can also be utilized in provide effect topicalantimicrobial activity and utilized in a method of treatment orprevention of a wide variety of affliction that are caused or aggravatedby microorganisms on for example the skin, mucous membranes, and/or oralcavity surfaces, including teeth. In some embodiments, the compositionmay be used when there are no clinical indications of an affliction.

The compositions can be delivered from swabs, brush, woven cloth,sponges, foams, fibers, and non-woven and paper substrates (e.g., papertowels and wipes). In typical embodiments, a sufficient amount of thecomposition is applied to a surface and allowed to remain on the surfacewhen applied in a dose, at a frequency, and in an amount sufficient toreduce or eliminate the microorganisms on the surface.

In another embodiment, a method of inhibiting biofilm formation on asurface of the oral cavity of a subject is described, comprising thesteps of (1) providing a composition as described herein, and (2)applying the composition to a surface in the oral cavity of a subject.The surface in the oral cavity of a subject includes, for example, abuccal surface, a gingival surface, a tooth, a dental restoration, andbone. The composition may be applied to the oral cavity of a subject by,for example, immersing, inserting, rinsing, spraying, brushing,swabbing, or combinations thereof. Spraying the composition may providethe composition in the form of, for example, an aerosol or a fine mist.The subject may be a human, or the subject may be a non-human animal.Non-human animals include mammals such as canines and felines.

In another embodiment, a kit is described comprising (1) a compositionas described herein, and (2) an application accessory. The applicationaccessory can be a container, a sprayer, a brush, a swab, a tray, andcombinations thereof. The application accessory can be any size. The kitmay include more than one application accessory or more than one kind ofapplication accessory (i.e., a sprayer and a brush). The kit may alsoinclude instructions for using the kit.

The compositions described herein are also useful for cleaning anddisinfecting hard surfaces. Such compositions are largely aqueous, andare readily pourable and pumpable when packaged from a manually operablepump, such as a ‘trigger spray’ dispenser. In some embodiments, thecleaned and disinfected article comprises a hard surface and the driedcomposition described herein. The dried composition may also providesome residual sanitizing activity.

Hard surfaces include for example, glass, ceramic (for example, ceramictile), cement, stone, porcelain, painted and/or clearcoat surfaces,appliances, plastic protective films which are backed withpressure-sensitive adhesives, metal (for example, architectural columns,plumbing fixtures), fiberglass, thermosetting polymers, sheet moldingcompound, thermoplastics (for example, polycarbonate, acrylics,polyolefins, polyurethanes, polyesters, polyamides, polyimides, phenolicresins, cellulose diacetate, cellulose triacetate, polystyrene, andstyrene-acrylonitrile copolymers), and combinations thereof. Additionalexemplary substrates include kitchen and bathroom hard surface such asbathtubs, toilets, sinks, faucets, mirrors, windows, and white boards.

Although care must still be taken to insure that the biguanideantimicrobial compound(s) are not inactivated by the inclusion ofadditional components, it is appreciated that cleaning and disinfectingcompositions for hard surfaces, rather than skin, can include a vastarray of additives that may not be suitable for skin contact uses.

The compositions can be applied to a surface of an article usingconventional coating techniques, such as brush, bar, roll, wipe,curtain, rotogravure, spray, or dip coating techniques. One method is toapply the composition using any suitable method and, after allowing aportion of the liquid to evaporate.

The compositions are suitable for use in a consumer “spray and wipe”application as a cleaning composition. In such an application, theconsumer generally applies an effective amount of the composition usingthe pump and within a few moments thereafter, wipes the treated areawith a cloth, towel, or sponge, typically a disposable paper towel orsponge. Such application materials may be hydrophilic or hydrophobic innature, preferably hydrophilic.

The composition described herein can also be applied to a hard surfaceby the use of a carrier substrate, as previously described. One exampleof a useful carrier substrate is a wet wipe. The wipe can be of a wovenor non-woven nature. Fabric substrates can include non-woven or wovenpouches, sponges including both closed cell and open celled sponges,including sponges formed from celluloses as well as other polymericmaterial, as well as in the form of abrasive or nonabrasive cleaningpads. Such fabrics are known commercially in this field and are oftenreferred to as wipes. Such substrates can be resin bonded,hydroentangled, thermally bonded, meltblown, needlepunched, or anycombination of the former. The carrier substrate useful with the presentinventive compositions may also be a wipe which includes a film formingsubstrate such as a water soluble polymer. Such self-supporting filmsubstrates may be sandwiched between layers of fabric substrates andheat sealed to form a useful substrate.

For antiseptic and cleaning uses, the compositions of the presentinvention are advantageously absorbed or disposed onto the carriersubstrate, i.e., a wipe to form a saturated wipe. The wipe can then besealed individually in a pouch which can then be opened when needed or amultitude of wipes can be placed in a container for use on an as neededbasis. The container, when closed, sufficiently sealed to preventevaporation of any components from the compositions. In use, a wipe isremoved from the container and then wiped across an area in need oftreatment; in case of difficult to treat stains the wipe may be re-wipedacross the area in need of treatment, or a plurality of saturated wipesmay also be used.

Objects and advantages of this disclosure are further illustrated by thefollowing non-limiting examples, but the particular materials andamounts thereof recited in these examples, as well as other conditionsand details, should not be construed to unduly limit this disclosure.

TABLE 1 MATERIALS Chemical Source DYNOL 604 SURFACTANT, 2,5,8,11- AirProducts and Tetramethyl-6-dodecyn-5,8-diol ethoxylate, Chemicals Inc.,Allentown, PA DYNOL 607 SURFACTANT Air Products and Chemicals Inc.SURFYNOL 104 SURFACTANT, 2,4,7,9- Air Products andTetramethyl-5-decyne-4,7-diol Chemicals Inc. SURFYNOL 485 SURFACTANT AirProducts and Chemicals Inc. Chlorhexidine gluconate (CHG) MPBiomedicals, Santa Ana, CA Polyhexamethylene biguanide (PHMB) LonzaChemicals, (Cosmocil CQ) Allendale, NJ SURFYNOL AD01 SURFACTANT, AirProducts and 2,4,7,9-Tetramethyldecane-4,7-diol Chemicals Inc.

Microbiological Methods

Staphylococcus aureus strain 15981 (Valle J et al. Mol Microbiol. 2003May; 48(4):1075-87) or Pseudomonas aeruginosa American Type CultureCollection strain number 9027 was grown to stationary phase in trypticsoy broth (Becton, Dickinson and Company, Franklin Lakes, N.J.) at 37°C. A volume of 2 mL of the stationary phase culture was centrifuged at13000 RPM for 5 minutes in an Eppendorf Microfuge centrifuge in order topellet the cells. The bacteria were then resuspended in 2 mL of sterile,deionized water, centrifuged again, and finally resuspended in 10 mL ofsterile, deionized water. A volume of 180 μl of each antimicrobialformulation was dispensed into a polystyrene 96 well plate intriplicate. 20 μl of the bacterial suspension was added to each wellcontaining antimicrobial formulations or control solutions for 15 to 60seconds. After the incubation period, 20 μl was removed from each welland transferred to 180 μl of Dey/Englay (D/E) broth (Becton, Dickinsonand Company, Franklin Lakes, N.J.) in order to neutralize antimicrobialmaterials. The bacteria in D/E broth were serially diluted 10-fold inphosphate buffered saline and 100 μl aliquots of each dilution weretransferred to 3M PETRIFILM AEROBIC COUNT PLATES (3M Co, St. Paul,Minn.). PETRIFILM plates were incubated for 24 hours at 37° C. andsurviving colony forming units (CFUs) were counted. The average log(CFU/mL) of surviving bacteria was calculated. Samples were performed intriplicate, unless otherwise noted. Accordingly, for each example,surfactants were diluted in deonized water and chlorhexidine gluconatewas added from a 20% stock solution when necessary.

Comparative Examples: C1-C3 Examples: Ex.1-Ex.2

The addition of SURFYNOL 104 to 0.1% CHG enhanced the ability of theformulation to kill gram positive bacteria, S. aureus as shown in Table2.

TABLE 2 Survival of S. aureus after 30 seconds and 60 seconds exposureto 0.1% CHG with varying concentrations of SURFYNOL 104 30 SecondsReduction 60 Seconds Reduction Ave. log Relative Ave. log RelativeEXAMPLES (CFU/mL) to Control (CFU/mL) to Control C1: 0.025% 9.43 None9.46 None SURFYNOL 104 C2: 0.0025% 9.50 None 9.33 0.06 SURFYNOL 104 C3:0.1% CHG 9.13 0.23 8.40 0.99 EX. 1: 0.025% 8.28 1.08 6.90 2.49 SURFYNOL104 + 0.1% CHG EX. 2: 0.0025% 8.64 0.72 7.85 1.54 SURFYNOL 104 + 0.1%CHG PBS (phosphate 9.36 9.39 buffered saline) control

Comparative Example: C4 Examples: Ex.3-Ex.6

The addition of DYNOL 604 or SURFYNOL 104 to 0.01% CHG enhanced theability of the formulation to kill P. aeruginosa in an exposure time of15 seconds as shown in Table 3.

TABLE 3 Survival of P. aeruginosa after 15 seconds exposure to 0.01% CHGwith varying concentrations of DYNOL 604 or SURFYNOL 104 ReductionAverage log Relative EXAMPLES (CFU/mL) to Control C4: 0.01% CHG 5.393.85 EX. 3: 0.25% DYNOL 604 + <3 >6.24 0.01% CHG EX. 4: 0.1% DYNOL 604 +<3 >6.24 0.01% CHG EX. 5: 0.025% SURFYNOL 104 + <3 >6.24 0.01% CHG EX.6: 0.0025% SURFYNOL 104 + 5.58 3.66 0.01% CHG PBS control 9.24 Limit ofdetection was 3 log (CFU/mL)

Comparative Examples: C5-C9 Examples: Ex.7-Ex.10

The addition of DYNOL 604 or DYNOL 607 to 0.1% CHG enhanced the abilityof CHG to kill S. aureus in a short period of time, as shown in Table 4.The surfactants alone at the same concentrations did not affect survivalof the bacteria, indicating a synergistic effect of the combination ofCHG and the nonionic surfactants.

TABLE 4 Survival of S. aureus after 30 seconds exposure to 0.1% CHG withvarying concentrations of DYNOL 604 or DYNOL 607 DYNOL DYNOL 604Reduction 607 Reduction Ave. log Relative Ave. log Relative EXAMPLES(CFU/mL) to Control (CFU/mL) to Control C5: 0.1% DYNOL 8.90 0.29 9.080.11 C6: 0.25% DYNOL 8.92 0.27 9.05 0.14 C7: 0.75% DYNOL 8.94 0.25 9.110.08 C8: 1.0% DYNOL 8.95 0.24 9.11 0.08 C9: 0.1% CHG 8.87 0.32 8.87 0.32(no surfactant) EX. 7: 0.1% DYNOL + <3 >6.19 <3 >6.19 0.1% CHG EX. 8:0.25% DYNOL + <3 >6.19 3.70 5.49 0.1% CHG EX. 9: 0.75% DYNOL + <3 >6.195.29 3.90 0.1% CHG EX. 10: 1.0% DYNOL + <3 >6.19 5.36 3.83 0.1% CHG PBScontrol 9.19 9.19 Limit of detection was 3 Log (CFU/mL)

Comparative Examples: C10-C13 Examples: Ex.11-Ex.14

The addition of ethanol to solutions of CHG and the nonionic surfactantsdid not disrupt the synergistic effect of their combination as shown inTable 5.

TABLE 5 Survival of S. aureus after 30 seconds exposure to 0.1% CHG pluseither 0.1% DYNOL 607 or 0.1% SURFONYL 485 in the presence of 5%ethanol. Reduction Ave. log Relative EXAMPLES (CFU/mL) to Control C10:0.1% CHG 7.82 0.62 C11: 0.1% CHG, 5% EtOH 7.17 1.27 C12: 0.1% SURFYNOL485 8.50 None EX. 11: 0.1% SURFYNOL 485, 7.44 1.00 0.1% CHG EX. 12: 0.1%SURFYNOL 485, 7.02 1.42 0.1% CHG, 5% EtOH C13: 0.1% DYNOL 607 8.51 NoneEX. 13: 0.1% DYNOL 607, 4.21 4.23 0.1% CHG EX. 14: 0.1% DYNOL 607, 3.814.63 0.1% CHG, 5% EtOH PBS control 8.44

Comparative Examples: C14-C18 Examples: Ex.15-Ex.18

SURFYNOL 104 was combined with polyhexamethylene biguanide (PHMB) andthe resulting combinations were tested for their ability to killbacteria growing in biofilms, communities of bacteria that attach tosurfaces. Bacterial biofilms were grown on a device that generates 96biofilms in a 96-well plate format. The biofilms are then exposed tovarious liquid formulations in a standard 96-well plate. It was observedthat SURFYNOL 104 enhanced the ability of PHMB to kill Pseudomonasaeruginosa in biofilms, as shown in Table 6.

Pseudomonas aeruginosa biofilms were grown in a Minimum BiofilmEradication Concentration (MBEC) device (Innovotech, Edmonton, AB,Canada). The MBEC device consists of standard polystyrene, 96-well plateand a polystyrene lid with attached pegs that protrude from the lid sothat they dip into the wells of the 96-well plate. Cultures of AmericanType Culture Collection (ATCC), Pseudomonas aeruginosa ATCC #15442 weregrown for 18 hours in trypticase soy broth (TSB, Becton Dickinson, andCompany, Franklin Lakes, N.J.) at 37° C. The 18 hour culture was diluted1:10,000 in fresh TSB and 150 μl of diluted culture was transferred toeach well of the MBEC device and the lid of the MBEC plate was placed onthe device so that the pegs of the lid dipped into the bacterialsuspension of the plate. The plate was then incubated for 24 hours at37° C.

After 24 hours, the lid of the MBEC device was transferred to a 96-wellplate containing 200 μl of sterile water in each well to remove anyloosely attached bacteria from the pegs of the MBEC device. Thebiofilm-covered pegs were then transferred to a 96-well plate containing200 μl of the exposure solutions in each well. The biofilms were exposedto the antimicrobial or control formulations for 6 minutes after whichthey were transferred to a new 96-well plate containing 210 μl ofDey/Englay neutralization broth (Becton, Dickinson, and Company,Franklin Lakes, N.J.) in each well. The bacteria were recovered from thedevice by sonication on a floating steel tray of a sonicating water bathfor 30 minutes (Branson Ultrasonics, Danbury, Conn.). After sonication,the bacterial suspensions were serially diluted 10-fold in a 96-wellplate and plated on 3M PETRIFILM AEROBIC COUNT PLATES (3M Co, St. Paul,Minn.). The plates were incubated for 48 hours at 37° C. The colonyforming units (CFUs) were enumerated and the average (triplicatesamples) log(CFU/peg) surviving in each exposure condition wascalculated.

TABLE 6 Survival of P. aeruginosa biofilms in MBEC Device after 6 minuteexposure to various concentrations of DYNOL 604 or SURFYNOL 104, + 0.1%PHMB Reduction Ave. log Relative EXAMPLES (CFU/mL) to Control Watercontrol 7.51 C14: 0.1% PHMB 5.52 1.99 C15: 0.1% DYNOL 604 6.98 0.53 C16:0.25% DYNOL 604 7.12 0.39 EX. 15: 0.1% DYNOL 604 + 0.1% PHMB 5.99 1.52EX. 16: 0.25% DYNOL 604 + 0.1% PHMB 5.85 1.66 C17: 0.025% SURFYNOL 1047.62 None C18: 0.0025% SURFYNOL 104 7.60 None EX. 17: 0.025% SURFYNOL104 + 0.1% 4.07 3.44 PHMB EX. 18: 0.0025% SURFYNOL 104 + 0.1% 4.69 2.82PHMB

Comparative Examples: C19-C22 Examples: Ex.19-Ex.20

The method of EX. 1-2 was used with the exception that SURFYNOL ADO 1was used instead of SURFYNOL 104 in the formulations. The addition ofSURFYNOL ADO 1 to 0.1% CHG enhanced the ability of the formulation tokill S. aureus in an exposure time of 30 seconds as shown in Table 7.

TABLE 7 Survival of S. aureus after 30 seconds exposure to 0.1% CHG pluseither 0.05% SURFYNOL AD01 or 0.1% SURFYNOL AD01. Reduction Ave. logRelative EXAMPLES (CFU/mL) to Control C19: 0.1% CHG 7.55 0.65 C20: 0.05%SURFYNOL AD01 8.09 0.11 C21: 0.1% SURFYNOL AD01 8.25 None C22: 1%SURFYNOL AD01 8.32 None EX. 19: 0.05% SURFYNOL AD01, 0.1% CHG 6.75 1.45EX. 20: 0.1% SURFYNOL AD01, 0.1% CHG 6.55 1.65 PBS control 8.20

1. An antimicrobial composition comprising an antimicrobial consistingof one or more biguanide compounds; and at least one hydrocarbonsurfactant enhancer having the formula

wherein L is a covalent bond or a saturated or unsaturated C₁-C₂ moiety,R is independently a straight chained or branched C₁-C₁₂ alkyl moiety, Xis independently a C₂-C₄ alkoxy, and m+n ranges from 0 to about 50; andwherein the biguanide antimicrobial compound(s) and surfactants(s) arepresent at a weight ratio ranging from 100:1 to 1:10.
 2. Theantimicrobial composition of claim 1 wherein the composition furthercomprises an aqueous or hydrophilic liquid carrier.
 3. The antimicrobialcomposition of claim 2 wherein the aqueous carrier comprises at least 50wt-% water.
 4. The antimicrobial composition of claim 1 wherein theaqueous or hydrophilic liquid carrier comprises an alkyl alcohol, etherglycol, or combination thereof.
 5. The antimicrobial composition ofclaim 1 wherein the composition further comprises a thickener.
 6. Theantimicrobial composition of claim 1 wherein the biguanide antimicrobialcompound is chlorhexidine gluconate (CHG) or polyhexamethylene biguanide(PHMB).
 7. (canceled)
 8. The antimicrobial composition of claim 2wherein the biguanide antimicrobial compound is present at aconcentration less than 5 wt-%.
 9. (canceled)
 10. The antimicrobialcomposition of claim 1 wherein the surfactant is present in an amountsuch that the antimicrobial activity of the biguanide antimicrobialcompound is improved.
 11. (canceled)
 12. The antimicrobial compositionof claim 1 wherein the hydrocarbon surfactant is an acetylenic diolsurfactant having the formula

wherein R is independently a straight chained or branched C₁-C₁₂ alkylmoiety, X is independently a C₂-C₄ alkoxy, and m+n is a number of molesof alkoxy and ranges from 0 to about
 50. 13. (canceled)
 14. An articlecomprising the composition of claim 1 absorbed or disposed on a carriersubstrate.
 15. The article of claim 14 wherein the carrier substrate isa swab, brush, woven cloth, sponge, foam, fiber, and non-woven or papersubstrate.
 16. A method of use comprising providing the composition ofclaim 1 and applying the composition to a surface.
 17. The method of useof claim 16 wherein the surface is mammalian skin, mucosal tissue, ororal cavity.
 18. The method of claim 16 wherein the surface is a hardsurface.
 19. The method of claim 16 wherein the surface is a kitchen orbathroom surface.
 20. The method of claim 18 further comprising and atleast partially removing the aqueous or hydrophilic liquid from thesurface of the substrate.
 21. An article comprising a hard surface andthe dried composition of claim 1.